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Molecular and Cellular Biology, March 2008, p. 1456-1469, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01510-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Basic Helix-Loop-Helix Transcription Factors Cooperate To Specify a Cortical Projection Neuron Identity{triangledown} ,{dagger}

Pierre Mattar, Lisa Marie Langevin, Kathryn Markham, Natalia Klenin, Salma Shivji, Dawn Zinyk, and Carol Schuurmans*

Institute of Maternal and Child Health, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada

Received 20 August 2007/ Returned for modification 26 September 2007/ Accepted 17 December 2007

Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only ~60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.

* Corresponding author. Mailing address: Institute of Maternal and Child Health, Hotchkiss Brain Institute, University of Calgary, 2277 HSC, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-3025. Fax: (403) 270-0737. E-mail: cschuurm{at}ucalgary.ca

{triangledown} Published ahead of print on 26 December 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2008, p. 1456-1469, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01510-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Roybon, L., Mastracci, T. L., Ribeiro, D., Sussel, L., Brundin, P., Li, J.-Y. (2009). GABAergic Differentiation Induced by Mash1 Is Compromised by the bHLH Proteins Neurogenin2, NeuroD1, and NeuroD2. Cereb Cortex 0: bhp187v1-bhp187 [Abstract] [Full Text]  


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